Macrolide antibiotics and the risk of ventricular arrhythmia in older adults

Abstract

Background: Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics.

Methods: We conducted a population-based retrospective cohort study involving older adults (age > 65 yr) with a new prescription for an oral macrolide antibiotic (azithromycin, clarithromycin or erythromycin) in Ontario from 2002 to 2013. Our primary outcome was a hospital encounter with ventricular arrhythmia within 30 days after a new prescription. Our secondary outcome was 30-day all-cause mortality. We matched patients 1:1 using propensity scores to patients prescribed nonmacrolide antibiotics (amoxicillin, cefuroxime or levofloxacin). We used conditional logistic regression to measure the association between macrolide exposure and outcomes, and repeated the analysis in 4 subgroups defined by the presence or absence of chronic kidney disease, congestive heart failure, coronary artery disease and concurrent use of a drug known to prolong the QT interval.

Results: Compared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia (0.03% v. 0.03%; relative risk [RR] 1.06, 95% confidence interval [CI] 0.83-1.36) and were associated with a lower risk of all-cause mortality (0.62% v. 0.76%; RR 0.82, 95% CI 0.78-0.86). These associations were similar in all subgroups.

Interpretation: Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated.

Figure 1:

Risk of 30-day hospital encounter with ventricular arrhythmia* associated with use of a macrolide antibiotic (azithromycin, clarithromycin or erythromycin) examined in subgroups defined by chronic kidney disease, congestive heart failure, coronary artery disease and use of a QT-prolonging drug. Data marker size is proportional to the inverse of the source variance. *Based on hospital presentation (emergency department visit or hospital admission) assessed by hospital diagnosis codes. Note: CI = confidence interval, RR = relative risk.

Figure 2:

Risk of 30-day all-cause mortality associated with use of a macrolide antibiotic (azithromycin, clarithromycin or erythromycin) examined in subgroups defined by chronic kidney disease, congestive heart failure, coronary artery disease and use of a QT-prolonging drug. Data marker size is proportional to the inverse of the source variance. Note: CI = confidence interval, RR = relative risk.